denifanstat (TVB-2640) / Sagimet Biosci, Ascletis - LARVOL DELTA

Real-world data comparison of asciminib 40 mg twice daily vs. 80 mg once daily in chronic myeloid leukemia patients (ASH 2025) - "Introduction: Asciminib (ASC) is a first-in-class Specifically Targeting the ABL Myristoyl Pocket (STAMP) inhibitor that binds to the ABL myristoyl pocket. In this real-world analysis, both ASC 40 mg BID and 80 mg QD demonstrated similar response rates and favorable AE profiles in CML-CP pts previously treated with ≥2 TKIs, with the limitation of a relatively small sample size. Overall efficacy was well maintained. The QD regimen was associated with fewer dose escalations and discontinuation rate, supporting its convenience and potentially advantageous dosing strategy in clinical practice."

Clinical • Real-world • Real-world evidence • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Musculoskeletal Diseases • Musculoskeletal Pain • Pancreatitis • Thrombocytopenia • ABL1

MAPK pathway-driven metabolic-inflammatory axis in AL amyloidosis (ASH 2025) - "Functional assays and lipidomic analysis wereconducted in ALMC1 cells using the FASN inhibitor TVB-2640 and the MEK inhibitor cobimetinib.ResultsLipidomic analysis of pre-treatment plasma samples revealed a significant increase in the lipogenesisindex in AL patients, indicating elevated FASN activity. This axissustains a pro-inflammatory environment that may contribute to disease pathogenesis. Thus, FASN andMAPK may represent promising metabolic-immunologic targets for therapeutic intervention in ALamyloidosis."

Amyloidosis • Hematological Malignancies • Metabolic Disorders • Multiple Myeloma • CCL2 • CCL3 • CXCL10 • CXCL8 • IFNG • IL13 • IL1B • SDC1

Asciminib and pregnancy in CML: Preliminary human data and clinical implications from 47 reported outcomes (ASH 2025) - "In the paternal exposure group, 8 men were receiving ASC asmonotherapy at the time of conception, while 5 were treated with ASC in combination with nilotinib orimatinib...In most cases, ASC hadbeen discontinued during the first trimester, often between 4 and 9W, with daily doses ranging from 20to 120 mg, and one ASC 40 QD+imatinib 400 mg...However, contraception is advised for women on ASC, especially if previouslyfailing other treatments; no contraception is needed for men. The presentation will provide updatedclinical details, including CML management during gestation and reproductive outcomes, offeringinsights to improve patient counseling, support informed reproductive choices, and guide personalizedtreatment."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Pneumonia • Respiratory Diseases • ABL1

High rates of deep molecular response (DMR) in patients (pts) with chronic myeloid leukemia in chronic Phase (CML-CP) who have not achieved dmr after ≥1 year of prior imatinib (IMA) in the asciminib (ASC) monotherapy arm of the Phase 2 ASC4MORE study (ASH 2025) - P2 | "In the phase 2ASC2ESCALATE study (NCT05384587), second-line ASC demonstrated high molecular response rates anda favorable safety profile, consistent with established ASC data across tx lines.The ASC4MORE study (NCT03578367) initially compared ASC 40 or 60 mg once daily (QD) add-on to IMA400 mg QD vs continued IMA 400 mg QD vs switch to nilotinib (NIL) 300 mg twice daily in pts with CML-CPnot achieving MR4 with ≥1 year of 1L IMA. No new or worsening safety signalswere observed compared with prior ASC studies and overall QOL improved or remained stable in mostpts. Results support early switching to ASC as an effective strategy to achieve DMR while maintainingfavorable safety/tolerability and QOL."

Clinical • Monotherapy • P2 data • Anorexia • Cardiovascular • Chronic Myeloid Leukemia • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Hypertension • Infectious Disease • Insomnia • Leukemia • Musculoskeletal Pain • Nephrology • Pancreatitis • Pulmonary Disease • Sleep Disorder

Ascletis Announces China National Medical Products Administration Acceptance of New Drug Application for Denifanstat (ASC40), a First-in-Class FASN Inhibitor for Acne Treatment (StockTitan.net) - "The company said denifanstat completed Phase II (NCT05104125) and Phase III (NCT06192264) studies, and in Phase III met all primary, key secondary and secondary efficacy endpoints (ITT analysis) versus placebo with a favorable safety profile and no related Grade 3/4 adverse events or related serious adverse events."

China filing • Acne Vulgaris

A Study to Evaluate Safety of ASC40 Tablets in Patients With Moderate to Severe Acne Vulgaris (clinicaltrials.gov) - P3 | N=240 | Completed | Sponsor: Ascletis Pharmaceuticals Co., Ltd. | Active, not recruiting ➔ Completed | Trial completion date: Mar 2026 ➔ Nov 2025

Trial completion • Trial completion date • Acne Vulgaris • Dermatology

Phase II Trial of the FASN Inhibitor, Denifanstat (TVB-2640), Plus Trastuzumab in Combination with Paclitaxel or Endocrine Therapy (ET) in Patients with HER2+ Metastatic Breast Cancer (MBC) Resistant to Trastuzumab (SABCS 2025) - "HP or H plus ET (fulvestrant or aromatase inhibitor) was administered at standard dose and schedule. Deni combined with HP provided clinical antitumor activity in pts with HER2+ MBC resistant to trastuzumab. Expected paclitaxel-associated AEs were observed. Nearly half of pts experienced a grade 3 or 4 AE attributed to the combination therapy, and 20% stopped treatment due to AE."

Clinical • Combination therapy • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • FAS • HER-2

Study of TVB-2640 in Men With Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Weill Medical College of Cornell University | Trial completion date: Nov 2026 ➔ Jan 2029 | Trial primary completion date: Nov 2025 ➔ Jan 2027

Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Neutrophil Extracellular Trap Reprograms Cancer Metabolism to Form a Metastatic Niche Promoting Non-Small Cell Lung Cancer Brain Metastasis. (PubMed, Adv Sci (Weinh)) - "Using an AI-driven prediction model and in vitro/in vivo assays, fatty acid synthase inhibitor TVB-2640 is identified as a potential therapeutic agent for disrupting metabolic vulnerability and suppressing NSCLC BMs. These findings provide novel insights into NET-dependent cellular interactions that sustain the pro-metastatic microenvironment underlying NSCLC BMs, offering robust development of novel metabolism-based therapeutic strategies to combat this lethal complication."

Journal • Brain Cancer • Lung Cancer • Metabolic Disorders • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • FASN • KRT10

Sagimet anticipates the data read out of its Phase 1 clinical trial to evaluate the PK and tolerability of a combination of denifanstat and resmetirom in the first half of 2026. (GlobeNewswire)

P1 data • Metabolic Dysfunction-Associated Steatohepatitis

Sagimet Biosciences Presents Two Denifanstat Posters at AASLD—The Liver Meeting 2025 (GlobeNewswire) - "In this qF4 subgroup, denifanstat treatment improved fibrosis by 1-2 qFibrosis stages with a response rate for ≥1 qFibrosis stage regression of 85% (11/13) for denifanstat vs. 33% (1/3) in placebo-treated patients...Additional findings: In F3 MASH patients, using clinical research network (CRN) scoring, the response rate for fibrosis improvement by ≥2 stages without worsening of MASH was 34% (16/47) for denifanstat, vs. 4% (1/23) in placebo-treated patients (p value = 0.0065); In qF4 MASH patients, using MASH CRN scoring, the response rate for fibrosis improvement by ≥1 stage was 39% (5/13) for denifanstat, of which 4/5 patients had 2 stages of improvement, vs. 0% (0/3) in placebo-treated patients...The second poster...Quantitative single-fiber traits and clustering revealed fibrosis phenotypes that predicted denifanstat response, supporting that computational pathology could be leveraged for response stratification."

P2b data • Metabolic Dysfunction-Associated Steatohepatitis

Sustained Efficacy and Safety with Asciminib (ASC) after Almost 4 Years of Median Follow-up from Ascembl, a Phase 3 Study of ASC Vs Bosutinib (BOS) in Patients (Pts) with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) after ≥2 Prior Tyrosine Kinase Inhibitors (TKIs): An End of Study Treatment (EOS Tx) Update, Including Results from Switch Population (ASH 2023) - " Adults (aged ≥18 y) with CML-CP after ≥2 prior TKIs, with intolerance or lack of efficacy per 2013 ELN recommendations were randomized 2:1 to receive either ASC 40 mg twice daily or BOS 500 mg once daily. With almost 4 y of follow-up in ASCEMBL, ASC continued to show greater efficacy and better safety/tolerability than BOS in pts with CML-CP after ≥2 prior TKIs. The robust safety profile of ASC was sustained through each analysis in ASCEMBL (wk 24, wk 96, and EOS Tx), confirming that pts receiving ASC can maintain a high level of response and continue Tx without experiencing late-emerging AEs. Results in the switch population support the use of ASC early in the Tx paradigm."

Clinical • P3 data • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Thrombocytopenia

Asciminib (ASC) in Combination with Imatinib (IMA), Nilotinib (NIL), or Dasatinib (DAS) May be a Potential Treatment (Tx) Option in Patients (Pts) with Philadelphia Chromosome–Positive Chronic Myeloid Leukemia in Chronic Phase or Accelerated Phase (Ph+ CML-CP/AP): Final Results from the Asciminib Phase 1 Study (ASH 2023) - P1 | "INTRODUCTION: ATP-competitive tyrosine kinase inhibitors (TKIs) have extended the life expectancy of pts with CML. ASC in combination with ATP-competitive TKIs, while associated with a higher AE burden vs ASC monotherapy, demonstrated rapid efficacy in the enrolled pt population. The MTD for ASC + IMA was reached at ASC 60 mg QD + IMA 400 mg QD (Table); the MTD for ASC + NIL or DAS was not reached. ASC 40 or 60 mg QD + IMA 400 mg QD, ASC 40 mg BID + NIL 300 mg BID, and ASC 80 mg QD + DAS 100 mg QD were recommended doses for expansion."

Clinical • Combination therapy • P1 data • Chronic Myeloid Leukemia • Fatigue • Hematological Malignancies • Leukemia • Oncology

Asciminib (ASC) Add-on to Imatinib (IMA) Demonstrates Sustained High Rates of Ongoing Therapy and Deep Molecular Responses (DMRs) with Prolonged Follow-up in the ASC4MORE Study (ASH 2023) - P2 | "Here, we report results of ASC add-on to IMA vs continued IMA vs switch to nilotinib (NIL) and of pts who crossed over from continued IMA to ASC add-on after 96 wks of Tx in pts not achieving DMR with ≥1 y of IMA as their first TKI (cutoff: 6 Mar 2023)...The top reasons for discontinuation were pt decision (9.5% with ASC 40 mg add-on), adverse events (AEs; 14.3% and 33.3%, with ASC 60 mg add-on and NIL, respectively), and physician decision (66.7% with IMA, all of whom crossed over to ASC 60 mg add-on)... Among pts not achieving DMR after ≥1 y on IMA, more pts achieved MR4.5 with ASC add-on to IMA than with continuing IMA or switching to NIL at wk 96. Pts crossing over from IMA to ASC 60 mg add-on were still able to achieve DMRs. ASC add-on to IMA was well-tolerated, with no new or worsening safety findings compared with those known for ASC alone."

Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Asciminib (ASC) Once-Daily (QD) Dosing Demonstrates Comparable Tolerability and Efficacy to Twice-Daily (BID) Dosing: Results from the ASC in Monotherapy 4 CML (AIM4CML) Study in Patients (Pts) with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) (ASH 2023) - P3 | "In the phase III ASCEMBL trial (NCT03106779) ASC 40 mg BID was well tolerated and demonstrated superior efficacy vs bosutinib 500 mg QD in pts previously treated with ≥2 TKIs, with major molecular response (MMR; BCR::ABL1IS ≤0.1%) rates of 25.5% vs 13.2% at wk 24 and 37.6% vs 15.8% at wk 96. This interim analysis of the AIM4CML trial further demonstrates the tolerability and efficacy of ASC and is among the first clinical reports on QD dosing of ASC in pts with CML-CP. Safety was comparable between the 80-mg QD and 40-mg BID doses, with both demonstrating safety profiles consistent with prior reports. Pts receiving ASC at both doses achieved and maintained molecular responses, which deepened over time."

Clinical • Monotherapy • Cardiovascular • Chronic Myeloid Leukemia • Cough • Fatigue • Hematological Malignancies • Hypertension • Infectious Disease • Leukemia • Musculoskeletal Pain • Oncology • Pain • Pulmonary Disease • Respiratory Diseases • Septic Shock

With up to 8 Years of Therapy, Asciminib (ASC) Monotherapy Demonstrated Continued Favorable Efficacy, Safety, and Tolerability in Patients (Pts) with Philadelphia Chromosome–Positive Chronic Myeloid Leukemia in Chronic Phase (Ph+ CML-CP) without the T315I Mutation: Final Results from the Phase 1 X2101 Study (ASH 2023) - "Based on safety, tolerability, efficacy, and pharmacokinetic data, ASC 40 mg BID was selected as the recommended dose for expansion in adults with CML-CP without the T315I mutation. In this final analysis of the phase 1 ASC trial in pts with CML-CP without the T315I mutation, ASC continued to show favorable efficacy and sustained safety and tolerability over a median exposure duration of 5.9 y, with a maximum exposure of 8.4 y. Pts achieved high rates of MMR with nearly one-fourth of pts achieving deep molecular responses at wk 96, demonstrating durable efficacy of ASC over time. Even with longer exposures, the risk of AEs did not increase and there were no new or worsening safety issues. With ASC, most AEs occurred early, and no new late-emerging safety issues were seen, supporting ASC as a safe and tolerable long-term Tx, highly clinically relevant in the management of resistant/intolerant CML-CP."

Clinical • Monotherapy • Chronic Myeloid Leukemia • Fatigue • Hematological Malignancies • Leukemia • Musculoskeletal Pain • Oncology • Pain

Impact of Mutations in Blood Cancer–Related Genes on Clinical Outcomes in Chronic Myeloid Leukemia in Chronic Phase (CML-CP) after ≥2 Tyrosine Kinase Inhibitors (TKIs) in the Ascembl Trial (ASH 2023) - "With >2 years of follow-up in the phase 3 ASCEMBL study, asciminib (ASC) has continued to demonstrate superior efficacy vs bosutinib (BOS) in pts with CML-CP after ≥2 prior TKIs, and analysis of cancer gene somatic mutations in this population has the potential to reveal additional insights into pts' response to study treatments or characteristics of the disease in later lines of therapy... Adults with CML-CP previously treated with ≥2 TKIs with intolerance of their last TKI or lack of efficacy per 2013 European LeukemiaNet recommendations and without BCR::ABL1 T315I or V299L mutations were randomized 2:1 to ASC 40 mg twice daily or BOS 500 mg once daily... ASXL1 mutations are most frequently detected at CML diagnosis and were enriched at BL in this study of pts with CML-CP previously treated with ≥2 TKIs, which is consistent with a role in TKI resistance. RUNX1 and IKZF1 mutations, which are associated with progression to accelerated or blast phase in CML, were..."

Clinical • Clinical data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • ASXL1 • IKZF1 • RUNX1

Sagimet Biosciences Announces Dosing of First Participants in Phase 1 PK Clinical Trial for Denifanstat and Resmetirom Combination (GlobeNewswire) - "Topline data from this trial are anticipated in the first half of 2026 and, if positive, are planned to be used to advance the development of the combination for patients living with metabolic dysfunction-associated steatohepatitis (MASH) into Phase 2, subject to consultation with regulatory authorities."

P1 data • Trial status • Metabolic Dysfunction-Associated Steatotic Liver Disease

Targeting the PI3K/AKT Pathway and Fatty Acid Synthase in AL Amyloidosis: Mechanistic Insights and Therapeutic Implications (ASH 2024) - "Furthermore, TVB-2640 (FASN inhibitor) was used to evaluate the cell response to FASN inhibition. Conclusions : Our findings highlight the significant upregulation of FASN in AL amyloidosis and its regulation by the PI3K/AKT pathway. The observed effects of Capivasertib on FASN expression and cell proliferation, along with the upregulation of inflammatory cytokines, underscore the potential for targeting the PI3K/AKT signaling pathway and FASN in developing more specific therapeutic strategies for AL amyloidosis."

Amyloidosis • Hematological Disorders • Hematological Malignancies • Monoclonal Gammopathy • Multiple Myeloma • Oncology • CXCL10 • FASN • LPIN1 • SDC1

Denifanstat for moderate-to-severe acne: A Phase 2, randomized, double-blind, placebo-controlled trial. (PubMed, J Eur Acad Dermatol Venereol) - P2 | "Denifanstat 50 mg once daily for 12 weeks was generally well tolerated and showed potential to reduce total lesion counts in moderate-to-severe acne vulgaris. Larger and longer term studies are needed to confirm efficacy and safety."

Clinical • Journal • P2 data • Acne Vulgaris • Conjunctivitis • Dermatology • Dry Eye Disease • Inflammation • Ocular Infections • Ocular Inflammation • Ophthalmology • FASN

A Phase III Randomized, Double-blind, Placebo-controlled, Multi-center Study to Evaluate Safety and Efficacy of ASC40 (Denifanstat) Tablets in Subjects With Moderate to Severe Acne Vulgaris (ChiCTR) - P3 | N=480 | Completed | Sponsor: Huashan Hospital, Fudan University; Huashan Hospital, Fudan University

New P3 trial • Acne Vulgaris • Dermatology

Denifanstat Achieved All Endpoints in the Treatment of Moderate to Severe Acne in Phase 3 Clinical Trial in Acne in China: A Presentation at the 2025 Fall Clinical Dermatology Conference (GlobeNewswire) - "Once daily oral 50 mg denifanstat achieved highly statistically significant and clinically meaningful improvements across all primary and secondary efficacy endpoints when analyzed using an intent-to-treat (ITT) analysis. At Week 12, treatment success rates with denifanstat were more than double those of placebo, with marked reductions in both inflammatory and non-inflammatory lesions. Denifanstat was generally well-tolerated....Ascletis announced completion of its pre-NDA consultation with China’s NMPA and its plans to submit an NDA for denifanstat in China."

China filing • P3 data • Acne Vulgaris

A Drug-Drug Interaction Study of Denifanstat and Resmetirom in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=40 | Active, not recruiting | Sponsor: Sagimet Biosciences Inc.

New P1 trial

Ascletis Pharma Inc…announces today that it recently completed the pre-New Drug Application (NDA) consultation with China National Medical Products Administration (NMPA) for denifanstat (ASC40) for the treatment of moderate-to-severe acne vulgaris and plans to submit an NDA soon. (The Manila Times) - "The pre-NDA consultation was initiated from June 2025 and completed in October 2025. Ascletis has completed the Phase II (NCT05104125) and Phase III (NCT06192264) studies of denifanstat (ASC40) for the treatment of moderate-to-severe acne vulgaris."

China filing • Acne Vulgaris

Sagimet Biosciences Inc…announced that analyses of the Phase 2b FASCINATE-2 study showing that denifanstat elicited fibrosis improvement in patients with advanced fibrosis will be presented at the American Association for the Study of Liver Disease (AASLD) - The Liver Meeting 2025, taking place November 7-11, 2025 in Washington, DC. (GlobeNewswire)

P2b data • Metabolic Dysfunction-Associated Steatohepatitis